KR102630604B1 - Device and method for immobilizing biomolecules using magnetic particles - Google Patents

Abstract

The present invention relates to a device for the reversible immobilization of biomolecules by magnetic particles (4), which includes a magnet (3) and containers (5, 51) that can be filled with a liquid containing biomolecules. A magnet 3 is provided in the container 5, 51 so that magnetic particles 4, which can be placed in the container 5, 51 and on which biomolecules can be fixed, especially reversibly fixed, are fixed in the container 5, 51. 51) are arranged on the table. An uneven magnetic field acting on the magnetic particles 4 located within the containers 5, 51 may be generated by the arrangement of the magnets 3, and as a result, the magnetic particles 4 may be structured by the influence of the uneven magnetic field. arranged in a certain way.

Description

Device and method for immobilizing biomolecules using magnetic particles

The present invention relates to a device for reversible immobilization of biomolecules according to the preamble of independent claim 1. The invention also relates to a method for reversible immobilization of biomolecules according to the preamble of independent claim 13. The invention also relates to a device for the automatic processing of biomolecules, comprising a device for reversible immobilization of biomolecules according to the preamble of independent claim 15.

Many methods for purification of DNA and other biomolecules are known in the art. One type of purification is DNA extraction, where the DNA is precipitated in a non-polar environment. DNA can also be purified, for example after cell disruption, by centrifugation, or by electrophoresis methods.

Biomolecules can also be synthesized and purified by immobilizing them on an insoluble carrier. A common substrate for immobilizing biomolecules is glass; less common substrates include gold, platinum, oxides, semiconductors, and various polymer substrates.

Because it takes too much time to manually refine and process numerous tasks, today's processes are fully automated. So-called “magnetic particles” play an important role in the automation of laboratory methods. “Magnetic bead-based cleaning” and “magnetic bead-based normalization” are widely used methods for immobilization, purification, and concentration adjustment of nucleic acids. Typical applications of these methods are sample preparation in DNA sequencing or DNA detection (e.g., by PCR, i.e. polymerase chain reaction).

In the prior art, magnetic particles are typically held within a container by a ring magnet surrounding the container. As a result, the solution containing impurities can be removed by pipetting (pipette off), while the magnetic particles and the biomolecules bound to them can remain in the container.

Magnetic particles were developed at the Whitehead Institute in 1995 for purification of PCR products. The magnetic particles are mostly paramagnetic and may consist of polystyrene coated with iron. A variety of molecules with carboxyl groups can be attached to iron. These carboxyl groups can reversibly bind to DNA molecules. In this way, the DNA molecules are immobilized.

Processes using magnetic particles typically include the following steps: First, the PCR product is bound to magnetic particles. The magnetic particles to which the PCR product is attached are then separated from impurities (this step is realized, for example, by pipetting off the solution from the solid). Next, the magnetic particles to which the PCR product is attached are washed. After washing, the PCR product is eluted from the magnetic particles and transferred to a new plate.

In a fully automated process, the starting material is introduced into the separation process and then the required reagents are automatically pipetted into the sample and removed again via the pipette tip. Magnetic particle-bound nucleic acids are collected at the bottom and edges of cavities and are re-dissolved by routine, optimized pipetting. Finally, the DNA or RNA is eluted into separate lidded containers for direct storage or further application.

Additionally, for example, an adsorption method in which DNA is bound to silica gel in a slightly acidic environment is known in the prior art.

One of the most important processes for the synthesis, normalization and purification of biomolecules is the process using magnetic particles. Here, biomolecules are bound to the surface of magnetic particles. The magnetic particles are then held in place by a magnet and the solution containing by-products and impurities can be easily separated. Therefore, biomolecules can be purified and separated quickly and easily. The advantage of magnetic globules is that they can move freely in the test configuration, which is important for the bonding step. For example, to remove liquid from a container during the cleaning step, simply attach a magnet to the container and then separate the liquid.

Magnetic particles are small paramagnetic or ferromagnetic spherules, coated with different materials that provide the necessary properties. Plastic-coated nickel particles are often used.

For example, DNA probes and genes can also be synthesized by automated solid-phase methods. DNA strands, such as polypeptides, can be synthesized by sequentially attaching activated monomers to a growing chain bound to an insoluble matrix (magnetic particle). Protected phosphoramidites can be used here as activated monomers.

This procedure can isolate high purity biomolecules in excellent yield. The basic process of magnetic particle separation can be performed fully automatically in the cavity of the used extraction vessel.

In a fully automated process, the starting material is introduced into the separation process and then the required reagents are automatically pipetted into the sample and removed again, for example by pipetting. Magnetic particle-bound nucleic acids are collected at the bottom and edges of the cavity and re-dissolved by routine optimized pipetting. Finally, the DNA or RNA is eluted into a separate container with a lid for direct storage or further application.

In the prior art, magnetic particles are typically held within a container by a ring magnet surrounding the container. As a result, the magnetic particles are arranged in a ring shape within the inner container.

A serious disadvantage of the prior art is that the magnetic particles in the container are also arranged in a ring shape due to the use of ring magnets. Not only does this make the liquid more difficult to remove, but it also means that there will still be liquid residue on the solid ring that cannot be removed. Incomplete removal of liquid reduces cleaning efficiency and available volume after elution.

Therefore, the object of the present invention is to provide a device for immobilizing biomolecules, a method for reversible immobilization of biomolecules, and a device for automatic processing of biomolecules that can avoid adverse effects known in the prior art. The device is provided.

This object includes a device for reversible immobilization of biomolecules having the features of independent claim 1, a method for reversible immobilization of biomolecules having the features of independent claim 13, and a device for reversible immobilization having the features of independent claim 15. This is achieved by a device for automatic processing of biomolecules.

According to the present invention, a device for reversible immobilization of biomolecules by magnetic particles is proposed. The device includes a magnet and a container that can be filled with a liquid containing biomolecules. A magnet can be placed within the container and a magnet is arranged on the container such that the biomolecules can be immobilized, in particular magnetic particles capable of being reversibly immobilized within the container. A non-uniform magnetic field acting on magnetic particles located within a container can be generated by the arrangement of magnets. Magnetic particles can be arranged in a structured way under the influence of a non-uniform magnetic field.

It is essential to the present invention that the arrangement of the magnets generates non-uniformity of the magnetic field. As a result, the arrangement of the magnets creates a non-uniform magnetic field that acts on the magnetic particles located in the container, and as a result, the structured arrangement of the magnetic particles within the non-uniform magnetic field allows the liquid to flow more easily away from the magnetic particles. there is. If magnetic particles controlled by a non-uniform magnetic field are arranged in isolated islands on the container wall, the liquid can simply flow out between the magnetic particles, and thus the liquid can be more easily removed from the container.

Within the framework of the present invention, the arrangement of magnets can be understood in a wide variety of designs. The arrangement of magnets refers to the function of generating a non-uniform magnetic field that acts on the magnetic particles in the container so that the magnetic particles are arranged in the structure according to the present invention on the wall of the container. By varying the magnet's flux density, the magnetic particles will align within the container so that the liquid can flow more easily and be more easily removed. The term “structure according to the present invention” refers to a structure that allows liquid to flow away more easily from the magnetic particles in the container. Therefore, for example, arranging magnetic particles into islands separated from each other can be understood as a “structure according to the present invention” or a “structured arrangement”, but the arrangement is not limited to this. The magnetic particles may also be arranged, for example in the form of a pyramid or in the form of a groove. Any structured arrangement of the magnetic particles on the vessel walls described above allows the liquid to easily flow from or between the magnetic particles. As an example of magnet array design, various ways to arrange magnets are as follows. Within the framework of the present invention, the arrangement of magnets can be understood as a special shape of the magnet, which may refer to the external design of a permanent magnet or to the winding of a coil in an electromagnet. Additionally, the arrangement of magnets can be understood as a magnetic conductive module that changes magnetic flux density and thereby generates a non-uniform magnetic field. The arrangement of magnets also involves arranging several magnets at a predetermined distance (distance from the container and distance between magnets) around the container, and causing the magnetic field in the form of a non-uniform magnetic field generated thereto to act on the magnetic particles in the container. I can understand. The heterogeneous magnetic field generated here acts more strongly on magnetic particles in some areas and less strongly on magnetic particles in other areas. Of course, the same effect occurs with other arrangements, since the magnetic field in some areas of the vessel acts more strongly on the magnetic particles within the vessel due to the shape of the magnetically conductive modules and magnets. These possibilities are explained in more detail through the following description and drawings. It should be noted again that structured arrangement does not mean a ring-shaped or similar arrangement of magnetic particles known in the prior art.

The magnets may also be movably arranged on the container such that the magnetic particles can move freely within the container during the reaction step and the magnetic particles are held in place by changing the position of the magnet in the container during the cleaning step. In particular, the magnet may be placed in a first position on the container to secure the magnetic particles, and the magnet may be moveable such that the magnetic particles can be moved by moving the magnet to a second position on or around the container. Of course, for example in automated devices, the container could also be moved relative to the magnet to achieve the same effect.

Within the framework of the present invention, the term 'biomolecule' refers to DNA, RNA, nucleic acids, proteins, and starting sequences for biomolecules, monomers or other biologically active molecules.

Hereinafter, the cleaning step is generally a process step in which liquid is discharged from the container by operating a valve and impurities of magnetic particles to which biomolecules are attached are separated. The cleaning step may also include cleaning with a cleaning solution (water or other).

Hereinafter, the reaction step is generally a process step in which the biomolecule bound to the magnetic particle is converted, bound to the particle, or extended (chain extension, e.g. PCR (“polymerase chain reaction”)).

Hereinafter, impurities are generally substances, solvents, by-products and contaminants that have not fully reacted or bound to the magnetic particles, as well as mixtures of two or more of those listed above.

Within the framework of the invention, a liquid may be a solution, in particular a reaction mixture of biomolecules and/or reagents and/or impurities.

Hereinafter, the magnetic particles may generally be particles in the micrometer or millimeter range. Magnetic particles can also be porous. Hereinafter, biomolecules generally have a thiol group and/or an amino group and/or a hydroxy group and/or a carboxyl group and/or a carbonyl group and/or an ester group and/or a nitrile group and/or an amine group and/or any It can be bound to the surface of magnetic particles through different functional groups. The magnetic particles may also be coated nickel particles or any other ferromagnetic or paramagnetic particles. Magnetic particles typically have a diameter of about 1 micrometer. Within the framework of the present invention, the term “about 1 micrometre” means between 0.5 and 1.5 micrometres, especially between 0.7 and 1.3 micrometres, and especially between 0.9 and 1.1 micrometres.

The advantages of the device according to the invention and the method according to the invention are as follows.

- Short processing time due to fast flow-off

- High yield

- purer product

- Efficient and economical

- Easy to automate

- Also for small sized devices

- Easy to modify existing machines

- Separation can be switched without moving disposables (with electromagnets alone)

In fact, the present device and method can be used for post-ligation purification.

The magnets of the device according to the invention can be designed as permanent magnets and/or electromagnets. While the shape of a permanent magnet affects the uniformity of its magnetic field, the uniformity of an electromagnet can be determined by its windings. Therefore, the shape of the permanent magnet can ensure that the magnetic field is non-uniform and that under its influence the magnetic particles are arranged in a structured manner. The term "arranged in a structured manner" may refer, for example, to an arrangement of several spatially separated islands through which liquid can escape and flow. However, when electromagnets are used, stronger magnetic fields can be generated here and there by more densely packed windings, thus also creating a non-uniform magnetic field that causes the magnetic particles to be arranged in a structured way.

The arrangement of the magnets may also be such that the magnets include a magnetically conductive module such that a non-uniform magnetic field is generated by the magnetically conductive module which acts on magnetic particles located in the container. Therefore, the magnetically conductive module must influence the magnetic field lines of the magnet's magnetic field so that the magnetic particles are arranged in the structure according to the invention. For this purpose, the magnetic field of the magnet at a predetermined point in the container can be amplified or attenuated by a magnetically conductive module, so that the magnetic particles are arranged more in the amplified area or less in the attenuated area of the container. In this way, alternating subregions can be created within the vessel using amplified or attenuated magnetic fields. Additionally, the magnetic conduction module may be considered to amplify the magnetic field of the magnet in a predetermined area and attenuate the magnetic field in the non-amplified area. The shape of the magnet may also be adjusted so that the magnetic field is amplified in predetermined areas of the container and attenuated in non-amplified areas.

Additionally, the magnetically conductive module can be arranged as a component on the magnet or the magnetically conductive module can be designed as an integrated element of the magnet. Accordingly, the magnetically conductive module may be an element attached to the magnet and disposed between the container and the magnet. In a ring magnet, for example, the magnetically conductive modules may be arranged as small rings with recesses or other modifications between the vessel and the magnets.

In general, the magnetically conductive modules can be arranged directly on the magnets or at a predetermined distance from the magnets. The magnet's uniform magnetic field is converted into a non-uniform magnetic field by the magnetic conduction module.

The magnetically conductive module may be designed as a magnetic amplification module and/or a diamagnetic module. The magnetic field of the magnet is amplified in a predeterminable area of the vessel by the magnetic amplification module, and the magnetic field of the magnet is attenuated in a predeterminable area of the vessel by the diamagnetic module. The diamagnetic module may also be designed with a plurality of diamagnetic shields arranged on the magnets such that the magnetic fields of the magnets within the container are weakened by the scattered shielding.

The diamagnetic module is composed of a diamagnetic material, such as graphite, with a relative permeability of less than one. The magnetic amplification module is comprised of ferromagnetic and/or paramagnetic materials with a relative permeability exceeding unity. Typical ferromagnetic materials are for example iron, nickel and cobalt. Typical paramagnetic materials are for example alkaline earth metals. In one embodiment of the invention, a mixture of magnetic amplification modules and diamagnetic modules may also be used, which modules have different diamagnetic and ferromagnetic/paramagnetic subranges.

In practice, the shape of the magnet can be adapted to the shape of the container so that the container can be inserted into the magnetically conductive module. Of course, the shape of the magnetically conductive module may be adapted to the container. Additionally, the magnet may include holes and/or recesses for inserting a container. The magnetically conductive module may include holes and/or recesses for inserting a container.

The container may be shaped in any way. In one embodiment of the invention, the vessel may be a multiwell plate, where the multiwell plate has a plurality of wells. Multiwell plates may in particular be microtiter plates. Particularly advantageously, the vessel may comprise a capillary tube, in which liquid with magnetic particles is retained by capillary forces and/or the liquid is removed by pressure.

Magnets may be placed in multiple wells of a multiwell plate. In this way, magnetic particles can be immobilized in multiple wells simultaneously.

The arrangement of the magnets is also designed so that a second magnet is arranged on top of the magnet so that the first magnetic field of the magnet is influenced by the second magnetic field of the second magnet, thus creating a non-uniform magnetic field that acts on the magnetic particles located within the container. It can be. When multiple permanent magnets are used as the second magnet, the permanent magnets may be arranged on the magnet such that the magnet's magnetic field is attenuated and/or amplified at some points. An electromagnet can also be used as a second magnet, which makes the magnetic field of the magnet non-uniform in the desired manner.

In one embodiment of the invention, the arrangement of the magnets may be designed such that the magnets have one or more notches such that a non-uniform magnetic field is generated by the notches in the magnets. A weak magnetic field is generated in the container at the notch location of the magnet, so that little or no magnetic particles are collected at the notch location.

In fact, the device may include a mechanism for removing the liquid, so that the liquid can be removed from the container after anchoring the biomolecules on the surface of the magnetic particles. The device for removing liquid may be a pipette, valve, compressed air, or other suitable device.

According to the present invention, a method for reversible immobilization of biomolecules is further proposed. The method includes the following steps. First, a liquid containing magnetic particles and biomolecules is placed in a container. The biomolecule is then bound to the magnetic particle, particularly reversibly bound.

Magnetic particles with immobilized biomolecules are immobilized in a container in a non-uniform magnetic field generated by an array of magnets, so that the magnetic particles are arranged in a structured manner. The liquid is then removed using a liquid removal device (where the liquid is separated from the magnetic particles by the structured arrangement of the magnetic particles and flows out), thereby leaving little or no liquid residue in the container and on the magnetic particles. There is nothing left at all. Biomolecules bound to magnetic particles can be separated from the surface of the magnetic particles and used further.

The above-described method is preferably carried out with a device according to the invention.

According to the invention, a device for automatic processing of biomolecules comprising a device according to the invention is also proposed. The method according to the invention can, for example, be carried out in a device for automatic processing of biomolecules. The advantage of such a device is that liquid with biomolecules and magnetic particles can be supplied to a vessel and removed from the vessel by suitable elements. Additionally, the position of the magnet on the container may be changed if necessary, for example to remove magnetic particles from the container. Multiwell plates are commonly used as containers in devices for automated processing of biomolecules.

Hereinafter, the present invention and prior art will be described in more detail using examples with reference to the drawings.

Figure 1 is a schematic diagram of a device for reversible immobilization of biomolecules with a multiwell plate and a magnetically conductive module.
Figure 2 is a schematic diagram of various types of magnets and magnetically conductive modules.
Figure 3 is a schematic diagram of another embodiment of a device for reversible immobilization of biomolecules.
Figure 4 is a schematic diagram of a magnet with a crown-shaped magnetically conductive module.
Figure 5 is a schematic diagram of the present invention and the prior art compared thereto viewed from above, and an embodiment of the present invention viewed from the side.
Figure 6 is a schematic diagram of a ring magnet with a magnetic amplification module and a magnetically conductive module as a diamagnetic module.

Figure 1 shows a schematic diagram of a device 1 for reversible immobilization of biomolecules with a multiwell plate 51 and a magnetically conductive module 2. In the depicted device (1), an array of magnets (3) consists of magnetically conductive modules (2). The magnetically conductive module 2 is arranged as an attachment on the magnet 3 so as to be positioned between the magnet 3 and the well 50 of the multiwell plate 51.

Due to the arrangement of the magnetically conductive module 2 and the magnet 3 described above, the magnetic particles 4 are arranged in a structured way within the container. In the operating state, after fixing the biomolecules to the surface of the magnetic particles, the liquid can be removed with a liquid removal device (not shown), and the liquid can simply flow between the structurally arranged magnetic particles.

Figure 2 shows a schematic diagram of various shapes of the magnet 3 and the magnetically conductive module 2. The magnet 3 can be designed as, for example, a crown-shaped magnet 201, a corrugated magnet 202 and a notched magnet 203. Of course, the magnetically conductive module can also be crowned or corrugated, or have a notch. Due to the crown shape, the magnetic particles are arranged into several isolated islands. The number of islands of magnetic particles corresponds to the number of teeth on the crown. The magnetic particles will also be arranged in waves in the same way. However, in the case of a notch, the magnetic particles will be arranged into two separate islands.

Figure 3 shows a schematic diagram of another embodiment of the device 1 for reversible immobilization of biomolecules. A container 5 is shown filled with a liquid 6 with biomolecules.

In operating conditions, the biomolecules will be anchored to the surface of magnetic particles (not shown). The liquid 6 will then be removed from the container.

Figure 3 also shows that magnets 3 with magnetically conductive modules 2 can be arranged on the container. Here, the magnetically conductive module 2 is designed as a crown-shaped attachment. Alternatively, a crown-shaped magnet 201 may be placed on the container. Both arrangements shown have a shape that matches the shape of the container 5 so that the container can be partially inserted into the magnet or magnetically conductive module.

Figure 4 shows a schematic diagram of a magnet with a crown-shaped magnetically conductive module 2. Here, the magnetically conductive module (2) is designed as an attachment to the magnet (3). The magnetically conductive module 2 has a hole 20 into which a container can be inserted for fastening.

Figure 5 is a diagram showing a comparison between the present invention (B) and the prior art (A) as seen from above in the container 5, and also schematically showing embodiments of the present invention (C) as seen from the side view of the container 5.

In the prior art (A), magnetic particles 4 are arranged in a ring shape at the edge of the container 5 by a uniform magnetic field of a magnet. Liquid cannot flow out and therefore remains in this ring during removal.

In the present invention (B), the magnetic particles 4 are arranged in a structured manner on the container wall by the non-uniform magnetic field of the magnet. By arranging the magnetic particles 4 into several separate islands as shown here, liquid can easily flow between the magnetic particles 4.

In part C of FIG. 5 , three embodiments of the possible arrangement of the magnetic particles 4 in a non-uniform magnetic field according to the invention on the container wall of the container 5 are shown. Arrangements of the magnetic particles 4 into several round islands, groove-shaped and pyramidal arrangements are shown. All of these arrangements are illustrative only and not limiting. Only various possibilities are mentioned. In the inhomogeneous magnetic field according to the invention, the magnetic particles can of course be arranged in any suitable structure allowing a simplified flow of liquid.

Figure 6 shows a schematic diagram of a ring magnet 3 with a magnetic amplifying module and a magnetically conducting module 2 as a diamagnetic module.

In part A of Figure 6, the magnetic conduction module 2 is a magnetic amplification module. The magnetic amplification module is configured as an insertion portion for the ring magnet (3) and is disposed between the ring magnet (3) and the container (5). Due to the magnetic amplification module, the magnetic field of the ring magnet 3 is further amplified and becomes non-uniform in the area without the gap 23. Accordingly, the magnetic particles 5 are structured and arranged on the wall of the container 5 between the gaps 23 .

In part B of Figure 6, the magnetically conductive module 2 is a diamagnetic module. The diamagnetic module is configured as an insert for the ring magnet (3) and is placed between the ring magnet (3) and the container (5). Due to the diamagnetic module, the magnetic field of the ring magnet 3 is attenuated more strongly in the area without the gap 23 and becomes non-uniform. Accordingly, the magnetic particles 5 are structured and arranged on the wall of the container 5 in the gap 23 .

Claims (15)

A device (1) for the reversible immobilization of biomolecules by magnetic particles (4), the device (1) comprising a magnet (3) and a container (5, 51) that can be filled with a liquid containing biomolecules. , a magnet 3 is provided in the container 5 so that magnetic particles 4, which can be arranged in the container 5, 51 and on which biomolecules can be fixed, especially reversibly fixed, are fixed in the container 5, 51. , 51) arranged on
An uneven magnetic field acting on the magnetic particles 4 located in the containers 5 and 51 can be generated by the arrangement of the magnets 3, and the magnetic particles 4 are moved to the container 5 by the influence of the uneven magnetic field. , 51) A device for the reversible immobilization of biomolecules, characterized in that it can be arranged as a plurality of isolated islands on the container wall, allowing liquid to flow between the isolated islands of said magnetic particles. 2. The arrangement of the magnets (3) according to claim 1, wherein the magnets (3) comprise a magnetically conductive module (2) so that a non-uniform magnetic field is generated by the magnetically conductive module (2) which acts on the magnetic particles located within the container. A device for reversible immobilization of biomolecules. 3. Reversible immobilization of biomolecules according to claim 2, wherein the magnetically conductive module (2) is arranged as one part on the magnet (3) or the magnetically conductive module (2) is designed as an integrated element of the magnet (3). device for. The device according to claim 2, wherein the magnetically conductive module (2) is a magnetic amplification module (21) and/or a diamagnetic module (22). 5. The method according to claim 1, wherein the shape of the magnet (3) is adapted to the shape of the container (5, 51) so that the container (5, 51) can be inserted into the magnetically conductive module (2). A device for reversible immobilization of biomolecules. The device according to any one of claims 1 to 4, wherein the vessel (5) is a multiwell plate and the multiwell plate has a plurality of wells. The device according to claim 6, wherein the magnets (3) are arranged in a plurality of wells of a multiwell plate. 5. Device according to any one of claims 1 to 4, wherein the magnet (3) comprises holes and/or recesses for inserting the container (5). 2. The method of claim 1, wherein a second magnet is disposed on the magnet (3) so that the first magnetic field of the magnet (3) can be influenced by the second magnetic field of the second magnet, so that within the container (5, 51) A device for reversible immobilization of biomolecules in which the magnets (3) are arranged so that a non-uniform magnetic field acting on the positioned magnetic particles can be generated. The method according to any one of claims 1 to 4, wherein the magnet (3) has a notch and the magnet (3) is arranged so that a non-uniform magnetic field can be generated by the notch of the magnet (3). A device for reversible immobilization of biomolecules. 5. Device according to any one of claims 1 to 4, wherein the magnets (3) are permanent magnets and/or electromagnets. 5. Device according to any one of claims 1 to 4, wherein the device (1) comprises a mechanism (6) for removing liquid. As a method for reversible immobilization of biomolecules,
a) placing a liquid (6) with magnetic particles (4) and biomolecules in a container (5, 51);
b) binding biomolecules to the magnetic particles (4), particularly reversibly binding them;
c) A step of fixing the magnetic particles (4) in the container (5) in the non-uniform magnetic field generated by the arrangement of the magnets (3), wherein the magnetic particles (4) are moved into the container (5, 51) arranged in a plurality of isolated islands on the vessel wall, so that liquid can flow between the isolated islands of said magnetic particles;
d) removing the liquid with a liquid removal device, wherein the liquid flows between the isolated islands of magnetic particles; and
e) A method for reversible immobilization of biomolecules, comprising the step of separating the biomolecules from the magnetic particles (4). 14. Method according to claim 13, wherein a device (1) according to any one of claims 1 to 4 is used. A device for the automatic processing of biomolecules, comprising the device (1) according to any one of claims 1 to 4.